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GeneBe

9-5339739-C-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006911.4(RLN1):c.8G>T(p.Arg3Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000526 in 1,613,456 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 28)
Exomes 𝑓: 0.00055 ( 2 hom. )

Consequence

RLN1
NM_006911.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.05
Variant links:
Genes affected
RLN1 (HGNC:10026): (relaxin 1) Relaxins are known endocrine and autocrine/paracrine hormones, belonging to the insulin gene superfamily. In humans there are three non-allelic relaxin genes, RLN1, RLN2 and RLN3, where RLN1 and RLN2 share high sequence homology. The protein encoded by this gene is synthesized as a single-chain polypeptide but the active form consists of an A chain and a B chain linked by disulfide bonds. Relaxin is produced by the ovary, and targets the mammalian reproductive system to ripen the cervix, elongate the pubic symphysis and inhibit uterine contraction. It may have additional roles in enhancing sperm motility, regulating blood pressure, controlling heart rate and releasing oxytocin and vasopressin. [provided by RefSeq, Jan 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.060755283).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RLN1NM_006911.4 linkuse as main transcriptc.8G>T p.Arg3Leu missense_variant 1/2 ENST00000223862.2
RLN1XM_047423703.1 linkuse as main transcriptc.8G>T p.Arg3Leu missense_variant 1/3
RLN1XM_047423706.1 linkuse as main transcriptc.-48+1082G>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RLN1ENST00000223862.2 linkuse as main transcriptc.8G>T p.Arg3Leu missense_variant 1/21 NM_006911.4 P1P04808-1

Frequencies

GnomAD3 genomes
AF:
0.000329
AC:
50
AN:
151794
Hom.:
0
Cov.:
28
show subpopulations
Gnomad AFR
AF:
0.0000487
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000706
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000231
AC:
58
AN:
251176
Hom.:
0
AF XY:
0.000236
AC XY:
32
AN XY:
135870
show subpopulations
Gnomad AFR exome
AF:
0.0000621
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000484
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000546
AC:
798
AN:
1461662
Hom.:
2
Cov.:
31
AF XY:
0.000536
AC XY:
390
AN XY:
727146
show subpopulations
Gnomad4 AFR exome
AF:
0.0000901
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000697
Gnomad4 OTH exome
AF:
0.000281
GnomAD4 genome
AF:
0.000329
AC:
50
AN:
151794
Hom.:
0
Cov.:
28
AF XY:
0.000283
AC XY:
21
AN XY:
74146
show subpopulations
Gnomad4 AFR
AF:
0.0000487
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000706
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000701
Hom.:
0
Bravo
AF:
0.000340
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.000239
AC:
29
EpiCase
AF:
0.000273
EpiControl
AF:
0.000356

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 03, 2021The c.8G>T (p.R3L) alteration is located in exon 1 (coding exon 1) of the RLN1 gene. This alteration results from a G to T substitution at nucleotide position 8, causing the arginine (R) at amino acid position 3 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.54
T
BayesDel_noAF
Benign
-0.61
Cadd
Benign
12
Dann
Benign
0.97
DEOGEN2
Uncertain
0.59
D
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.0040
N
LIST_S2
Benign
0.44
T
M_CAP
Benign
0.0061
T
MetaRNN
Benign
0.061
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
2.0
M
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.29
T
PROVEAN
Uncertain
-3.6
D
REVEL
Benign
0.020
Sift
Benign
0.033
D
Sift4G
Benign
0.092
T
Polyphen
0.020
B
Vest4
0.094
MVP
0.25
MPC
0.45
ClinPred
0.11
T
GERP RS
-4.7
Varity_R
0.094
gMVP
0.35

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs138075606; hg19: chr9-5339739; API